PWWP2B

Chr 10

PWWP domain containing 2B

Also known as: PWWP2, bA432J24.1, pp8607

NCBI Gene: 170394 ENSG00000171813 UniProt: Q6NUJ5 OMIM: 621586

PWWP2B encodes a chromatin-binding protein that acts as an adapter between nucleosome components and chromatin-modifying complexes, regulating histone acetylation levels at actively transcribed genes by forming NuRD subcomplexes and recruiting HDACs to gene promoters. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay. The gene follows autosomal dominant inheritance and is highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Enables NuRD complex binding activity. Predicted to be involved in chromatin remodeling; positive regulation of transcription elongation by RNA polymerase II; and regulation of cold-induced thermogenesis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.49

Clinical Summary— PWWP2B

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.84) — some intolerance to loss-of-function variants.

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ClinVar Variants

124 VUS of 145 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.841

Z-score 2.28

OE 0.00 (0.00–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.42Z-score

OE missense 0.81 (0.74–0.88)

338 obs / 419.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.49)

0≤0.351.4

Missense OE?0.81 (0.74–0.88)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 0 / 6.0Missense obs/exp: 338 / 419.6Syn Z: -1.92

This gene — mechanism propensity

0.2997th %ile

GOF

0.2497th %ile

LOF

0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.49

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

145 submitted variants in ClinVar

ClinVar

Classification Summary

VUS124

Likely Benign10

124

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	0	124	124
Likely Benign	1	9	10
Benign	0	0	0
Total	1	133	134

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

98 pathogenic / likely-pathogenic (of 110) ClinVar copy-number / structural variants overlap PWWP2B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →